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September 16, 2019

Research breathes new air into donor lungs

By Advancing the Science contributor

Ex vivo lung perfusion technology is the process by which marginal donor lungs are treated with specialized solutions and gases that can reverse lung injury and remove excess fluids in the lung, making them clinically viable for transplant.

By Sara Nick

Four hundred: That’s the number of U.S. patients who die each year awaiting a lung transplant, or are removed from the wait list when they become too ill. Now, cutting-edge research underway on Mayo Clinic’s Florida campus aims to save as many of those lives as possible. “We’re hoping to wipe out the wait list and get that number as close to zero as possible,” says Mayo pulmonologist David Erasmus, M.B., Ch.B., M.D.

“Lungs are very delicate,” Mayo pulmonologist Jorge Mallea, M.D., says of the shortage. “Of all available organ donors, only about one in five can donate their lungs, which suffer greatly from the effects of brain death.” Additionally, he explains, it can be difficult for a medical team to predict whether a particular set of donor lungs can be successfully transplanted. “The goal of our research is to address these challenges. In doing so, we can increase the number of lungs available for donation,” he says.

Newly opened Discovery and Innovation Building on Mayo Clinic's Jacksonville, Florida, campus.

At the center of this research is a recently developed technique called ex vivo lung perfusion. In this approach, a lung is removed from its donor, isolated, and placed in a specialized chamber where it is resuscitated and supported, making otherwise marginal donor lungs suitable for transplant. The process also allows experts to better predict whether donor lungs will be successful in transplant.

“Will donor lungs cared for in a
centralized system be just as good as — and ideally better than — those in the
traditional donor program? That’s the question our research is getting at,”
says Dr. Mallea.

The lung perfusion platform has already
been shown to be safe, so Mayo researchers are now looking at ways to maximize
its reach for the benefit of patients across the country. Currently, each
hospital that wants to use ex vivo lung perfusion for patients must have its
own equipment, staff, and space. “This is expensive and inefficient,” says Dr.
Mallea. Instead, they’re assessing whether a centralized system for lung
perfusion can better serve the needs of patients and hospitals. Under this
approach, donor lungs from any part of the country could be shipped to a
dedicated facility, cared for and evaluated by lung perfusion experts, and sent
back to recipient patients at any participating hospital.

Lung Bioengineering Center in the Discovery and Innovation Building in Jacksonville, Florida.

The scientists are collaborating with biotechnology company United Therapeutics. On August 22, Mayo and United Therapeutics celebrated the grand opening of a new lung bioengineering center on Mayo’s Florida campus.

Evaluating a centralized facility for ex vivo lung perfusion is just one aspect of the expansive lung transplant research scene on Mayo’s Florida campus. For example, Dr. Erasmus and colleagues are collaborating with a team from the University of Vienna to assess whether a new biomarker can be used to determine transplant recipients’ level of immunosuppression.

“If patients are overly immunosuppressed, they’re more susceptible to infection; if they’re under-suppressed, they’re more likely to reject the organ,” Dr. Erasmus explains. “This biomarker could help us adjust their medications accordingly, which is currently difficult to do.”

Additionally, in the field of regenerative medicine, Dr. Erasmus, Abba Zubair, M.D., Ph.D., and colleagues are working to determine whether bone-marrow derived mesenchymal stem cells can be administered to transplant recipients to prevent chronic organ rejection. The scientists also hope that stem cells could one day be applied during ex vivo lung perfusion can improve lungs’ suitability for transplant. “Mayo can offer patients everything from at-home pulmonary rehab exercises all the way through lung transplant,” says Dr. Mallea. “Stem cell therapy would allow Mayo to complete the whole gamut of treatment.”

“Mayo has always been at the forefront
of clinical medicine, and we’re in the midst of an incredible opportunity to
spearhead the area of lung transplant,” Dr. Erasmus adds. “This work can make a
significant difference for patients.”